title: Novel N-4-piperazinyl-ciprofloxacin-chalcone hybrids: synthesis, physicochemical properties, anticancer and topoisomerase I and II inhibitory activity.
abstract: A group of novel N-4-piperazinyl-ciprofloxacin-chalcone hybrids was prepared. One-dose anticancer test results indicated that compounds 3a and 3g exhibited the highest ability to inhibit the proliferation of different cancer cell lines. Compound 3a exhibited a broad-spectrum of anti-tumor activity without pronounced selectivity while compound 3g revealed high selectivity toward the leukemia subpanel with selectivity ratio of 6.71 at GI₅₀ level. Moreover, compounds 3e and 3j have shown remarkable topo II inhibitory activity compared to etoposide at 100 μM and 20 μM concentrations. Compounds 3e and 3j exhibited comparably potent topo I inhibitory activity at 20 μM concentration compared to camptothecin. Compounds 3e and 3j exhibited strong topo II inhibitory activities compared to topo I at 20 μM concentration. Studying of the solubility and partition coefficient revealed higher lipophilicity of the hybrids 3a-j compared to the parent ciprofloxacin.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, 61519 Minia, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Aziz
authors.forename: So-Eun
authors.initials: SE
authors.lastname: Park
authors.forename: Gamal El-Din A A
authors.initials: Gel-D
authors.lastname: Abuo-Rahma
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Sayed
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000737:chemistry*; D002939:Ciprofloxacin / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D002939:Ciprofloxacin; D002599:Chalcone; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II
keywords: Anti-tumor; Chalcone; Ciprofloxacin; Hybrids; Topoisomerase